Dr Maksimovic on a Novel Preclinical Model of Bone Metastasis in ccRCC

Stefan Maksimovic, MD, postdoctoral fellow, The University of Texas MD Anderson Cancer Center, discusses the preclinical investigation of innovative tissue engineering with optical windows, state-of-the-art fluorescence reporter technology, and intravital multiphoton microscopy in mouse models with clear cell renal cell carcinoma (ccRCC).

Approximately 80% of renal neoplasms are categorized as ccRCC, with bone being a primary site for distant metastasis. Bone metastases in patients with ccRCC can cause various skeletal complications, negatively impacting quality of life and survival outcomes for patients with this disease. Therefore, trial investigators aimed to establish a novel approach to studying and modeling bone metastasis in mice, Maksimovic begins. This approach featured a tissue-engineered bone construct with an implanted window model, allowing intravital multiphoton microscopy to monitor ccRCC lesions longitudinally. The purpose of the model was to offer valuable insights into the mechanistic and applied aspects of therapy response in bone metastasis.

Several obstacles were encountered when studying this approach, including difficulties creating a bone metastatic niche in mice while preserving their immune system. Additional considerations were necessary to optimize the mice environment without compromising the immune system when assessing drug efficacy in bone metastasis using human cell lines, Maksimovic emphasizes.

The primary focus of the investigation was to longitudinally monitor the same lesion's development over time, particularly when evaluating tumor responses with select therapies, he expands. Researchers set out to create a model that captures details from the metastatic niche while maintaining and mirroring the components of a healthy adult with an intact immune system, Maksimovic notes. Notably, this model allows for the creation of live metastasis, eliminating the need for sacrifice during analysis. This, in turn, enables investigators to explore various therapeutic approaches and observe their impact on the same lesion over time, he concludes.